This application is in response to PA-07-126 "Women's Mental Health and Sex/Gender Differences Research." The PA calls for studies of neurobiological, sex hormone, and genetic factors contributing to sex differences in the prevalence and etiology of mental disorders. Bulimic syndromes are much more prevalent in women than men and may exhibit genetic influence only after sex hormone activation. The long-term objective of this project therefore is to identify a novel set of neurobiological mechanisms that contribute to genetic influences on bulimic syndromes in women. The specific aims are to examine: 1) phenotypic relationships between changes in ovarian hormone levels and changes in disordered eating across the menstrual cycle in a large sample of female twins;and 2) whether a common set of genetic factors underlie associations between ovarian hormones and binge eating. Participants will include 590 same-sex female twins recruited through birth records in Michigan. Structured clinical interviews will be administered to assess eating disorders and other Axis I disorders. Daily salivary hormone samples and behavioral measures of binge eating and mood symptoms will be collected for 45 days. Radioimmunoassay will be used to analyze estradiol, and enzymeimmunoassay will be used to analyze progesterone. Dynamical systems models will examine the extent to which changes in ovarian hormones predict changes in binge eating across the menstrual cycle. Genetic mediation of these phenotypic associations will be examined by incorporating twin pair information into analyses using bivariate and multivariate genetic models. The proposed set of studies follow recommendations of Becker et al. (2005) to use naturalistic, longitudinal studies across the menstrual cycle to establish associations between ovarian hormones and binge eating before attempting experimental designs in humans. We propose to extend this approach by examining whether these naturalistic associations have a genetic component. Findings from our multi-method studies have the potential to significantly increase understanding of the causes of bulimic syndromes in women by seeking the underlying neurobiological mechanisms contributing to their genetic diathesis. Greater insight into etiological mechanisms will narrow the search for candidate genes and contribute to improved treatment and prevention of these disorders. PUBLIC HEALTH RELEVANCE: Bulimic syndromes are significant mental health problems that preferentially afflict late adolescent and young adult women. The pronounced psychiatric and medical morbidity associated with these disorders underscore their public health significance and the need to understand their development. Greater insight into neurobiological mechanisms will narrow the search for candidate genes and contribute to improved treatment and prevention of these disorders.